1. Field of the Invention
The body is capable of both specific immune response and non-specific immune response in dealing with non-self antigens. The body's specific immune response consists mainly in either producing antibodies or receptor cells. Non-specific immune response consists of phagocytosis of bacterial and other particles. Both types of immunity are important in protecting the body from infecting organisms and in maintaining the integrity of the body.
There are a number of circumstances where the body's response to infecting organisms or antigens is deficient. Congenital or acquired immune deficiency, failure to distinguish self and non-self antigens, transplantation of immunologically incompatible organs, destruction of the hemopoietic system where bone marrow tissue replacement is from a non-identical donor (graph versus host disease) are all examples of situations where the body's response is inadequate.
A relatively new drug for treatment of pharmacological immunosuppression is cyclosporin, particularly, cyclosporin A. Cyclosporin A is an extremely hydrophobic cyclic peptide consisting of 11 amino acids with a molecular weight of approximately 1,200. Cyclosporin A suppresses humoral as well as cell mediated immunity in all animal species tested to this point, including humans. The drug may be administered both parenterally or orally. The immunosuppressant effects of cyclosporin A have been demonstrated. Cyclosporin A could be potentially useful in several types of organ transplantation, various autoimmune diseases, and possibly rheumatory arthritis.
In administering a cyclosporin, it is frequently necessary to insure that the blood level of the cyclosporin remains within a certain narrow concentration range in order to insure effective dosage, while avoiding levels which may be toxic or produce undesirable effects. Furthermore, it is often necessary to detect potentially toxic levels of cyclosporin.
It is, therefore, desirable to provide a simple and rapid procedure for determining or detecting the levels of cyclosporin in serum or other physiological fluids. The procedure should provide reproducible values and be specific for the cyclosporin which is measured. Thus the procedure must be capable of distinguishing cyclosporin from other drugs, which would otherwise give an erroneous result in an assay for the detection of a cyclosporin.
2. Brief Description of the Prior Art
A method for the total synthesis of cyclosporins, novel cyclosporins, and novel intermediates and methods for their production are described in U.S. Pat. Nos. 4,396,542 and 4,554,351. A synthesis of enantiomerically pure (2S, 3R, 4R, 6E)-3-hydroxy-4-methyl-2-methylamino- 6-octenoic acid starting from tartaric acid is disclosed by Wenger in Helvetica Chimica Acta (1983) 66:2308-2321.